The autonomic nervous system (ANS) is a very complex, multifaceted neural network that

maintains internal physiologic homeostasis. This network includes cardiovascular,

thermoregulatory, GI, genitourinary (GU), and ophthalmologic (pupillary) systems (see the
following image). Given the complex nature of this system, a stepwise approach to autonomic
disorders is required for proper understanding.

Autonomic nervous system.

The goal for this article remains focused at step III on the anatomy of the autonomic nervous
system, as follows.

Step I - Understand the reason for testing

Step II - Recognition and etiology (especially small fiber neuropathy [SFN])

Step III - Understand basic anatomy and neurophysiology

Step IV - Learn the methods for testing

Step V - Diagnosis and management

Almost 10% of the population (or > 30 million people in the US) may acquire an autonomic
disorder requiring medical attention. Because the autonomic nervous system maintains internal
physiologic homeostasis, disorders of this system can be present with both central as well as
peripheral nervous system localization.

Causes of ANS dysfunction

The etiology of autonomic dysfunction can be primary or idiopathic and secondary causes.
Autonomic failure is seen in multiple system atrophy, pure or progressive autonomic failure,
Parkinson and other neurodegenerative diseases, metabolic diseases such as Wernicke and
cobalamin deficiency, diabetes mellitus, hyperlipidemia, trauma, vascular diseases, neoplastic

diseases, and multiple sclerosis. In addition, autonomic dysfunction is associated with various
medications.
In addition to diabetes, autonomic dysfunction is associated with other neuropathies, including
Guillain-Barr syndrome, Lyme disease, human immunodeficiency virus (HIV) infection,
leprosy, acute idiopathic dysautonomia, amyloidosis, porphyria, uremia, and alcoholism. Besides
nerve localization in the peripheral nervous system, it occurs in diseases of the presynaptic
neuromuscular junction such as botulism and myasthenic syndrome.
In addition to the acquired causes, inherited disorders like hereditary sensory-autonomic
neuropathy (HSAN), familial amyloid polyneuropathy (FAP), Tangier disease, and Fabry disease
also exist.

Clinical presentation
Clinically, postural lightheadedness, dry mouth, dry eyes, impotence, loss of sweating or
hyperthermia, nocturnal diarrhea, gastroparesis, impaired accommodation, urinary or bowel
incontinence, and small fiber neuropathy are some of the presenting symptoms. Most peripheral
neuropathies affect all fiber sizes. Few peripheral neuropathies are associated with pure or
predominantly small fiber involvement. A large proportion is associated with diabetes. Painful
burning feet is caused by a sensory neuropathy with small fiber involvement in more than 90%
of cases. Patients with pure small fiber involvement display normal large fiber function. Muscle
bulk, strength, muscle stretch reflexes, and large fiber sensory function (ie, vibration,
proprioception) are normal.

Myelinated vs unmyelinated small fibers

Small fibers are both myelinated and unmyelinated. Small myelinated fibers transmit
preganglionic autonomic efferents (B fibers) and somatic afferents (A delta fibers).
Unmyelinated (C) fibers transmit postganglionic autonomic efferents as well as somatic and
autonomic afferents. Both A delta and C fibers are widely distributed in skin and deep tissues.
The neurotransmitter for preganglionic sympathetic and parasympathetic nervous system (PNS)
as well as postganglionic parasympathetic nervous system is acetylcholine (ACh). The
neurotransmitter for the postganglionic sympathetic nervous system (innervating sweat glands) is
also acetylcholine, whereas that for the remaining postganglionic sympathetic nervous system is
norepinephrine (NE).

Electromyography
Electromyography (EMG) plays a key role in the evaluation of most peripheral neuropathies and
helps in assessing only large myelinated fibers. Thus, pure small fiber neuropathies may be
associated with normal findings on routine electrophysiologic studies. Elderly patients who lack
sural sensory responses can still be diagnosed with small fiber neuropathy. Patients with
symptoms other than neuropathic ones certainly need autonomic function testing for appropriate
diagnosis.